The basis of this proposal is to investigate the molecular biology of antibody-associated paraneoplastic syndromes. Although rare, these neurological syndromes are of crucial importance since the patients harbor high-titer antibodies directed against human tumor antigens. Three antibody-associated paraneoplastic neurological syndromes which have been discovered and characterized in this laboratory will be further investigated at the molecular level. These syndromes include: the Yo syndrome associated with cerebellar dysfunction and antibodies directed against ovarian tumor antigens; the Hu syndrome associated with sensory neuronopathy and antibodies directed against small cell lung cancer antigens; the Ri syndrome associated with opsoclonus and antibodies directed against breast tumor antigens. The availability of these high-titer human antibodies provide a unique opportunity to: (a) Isolate human tumor antigens (b) Investigate tumor specific gene expression mechanisms. (c) Understand the molecular basis of the human anti-tumor immune response.